tbuckley/cabot-search huggingface dataset:
DNA replication: Mechanisms and therapeutic interventions for diseases
Authors: Hao‐Yun Song, Rong Shen, Hamid Mahasin, Ya‐Nan Guo, De‐Gui Wang
Journal: MedComm (2023)

Abstract Accurate and integral cellular DNA replication is modulated by multiple replication‐associated proteins, which is fundamental to preserve genome stability. Furthermore, replication proteins cooperate with multiple DNA damage factors to deal with replication stress through mechanisms beyond their role in replication. Cancer cells with chronic replication stress exhibit aberrant DNA replication and DNA damage response, providing an exploitable therapeutic target in tumors. Numerous evidence has indicated that posttranslational modifications (PTMs) of replication proteins present distinct functions in DNA replication and respond to replication stress. In addition, abundant replication proteins are involved in tumorigenesis and development, which act as diagnostic and prognostic biomarkers in some tumors, implying these proteins act as therapeutic targets in clinical. Replication‐target cancer therapy emerges as the times require. In this context, we outline the current investigation of the DNA replication mechanism, and simultaneously enumerate the aberrant expression of replication proteins as hallmark for various diseases, revealing their therapeutic potential for target therapy. Meanwhile, we also discuss current observations that the novel PTM of replication proteins in response to replication stress, which seems to be a promising strategy to eliminate diseases.
Table of Contents
Authors: Rashad Sami Barsoum, Saraladevi Naicker, Mohamed Hany Hafez, John Dirks, Peter Reese, Bruce Gelb, Griffith Perkins, Shane Grey, P Coates, Nora Franceschini, Jonathan Berg, Franck Bihl, Gérard Lambeau, Rebecca Johnson, Bradley Warady, Pavel Roshanov, Amit Garg, Fadi Fakhouri, Nora Schwotzer, Gianfranca Cabiddu, Jonathan Barratt, Hélène Legardeur, Vesna Garovic, Alejandra Orozco-Guillen, Jack Wetzels, Eric Daugas, Gabriella Moroni, Marina Noris, Vincent Audard, Manuel Praga, Elisa Llurba, Grégoire Wuerzner, Rossella Attini, David Desseauve, Elena Zakharova, Claudio Luders, Kate Wiles, Filomena Leone, Shilpanjali Jesudason, Nathalie Costedoat-Chalumeau, Andrea Kattah, Virgilia Soto-Abraham, Alexandre Karras, Jai Prakash, Liz Lightstone, Pierre Ronco, Claudio Ponticelli, Gerald Appel, Giuseppe Remuzzi, Vassilis Tsatsaris, Barbara Piccoli, Sandra Rayego-Mateos, Raul Rodrigues-Diez, Beatriz Fernandez-Fernandez, Carmen Mora-Fernández, Vanessa Marchant, Javier Donate-Correa, Juan Navarro-González, Alberto Ortiz, Marta Ruiz-Ortega
Journal: Kidney International (2023)
Co-delivery of microRNA-150 and quercetin by lipid nanoparticles (LNPs) for the targeted treatment of age-related macular degeneration (AMD)
Authors: Wei Li, Liang Chen, Zhongwei Gu, Zhoujiang Chen, Hong Li, Zhongxia Cheng, Hanmei Li, Liang Zou
Journal: Journal of Controlled Release (2023)
μ‐opioid receptor agonist facilitates circulating tumor cell formation in bladder cancer via the MOR/AKT/Slug pathway: a comprehensive study including randomized controlled trial
Authors: Xiaoqiang Wang, Song Zhang, Di Jin, Jiamei Luo, Yumiao Shi, Yiqi Zhang, Lingling Wu, Yanling Song, Diansan Su, Zhiying Pan, Haige Chen, Ming Cao, Chaoyong Yang, Weifeng Yu, Jie Tian
Journal: Cancer Communications (2023)

μ-opioid receptor agonists (MORAs) are indispensable for analgesia in bladder cancer (BC) patients, both during surgery and for chronic pain treatment. Whether MORAs affect BC progression and metastasis remains largely unknown. This study focused on the effects of MORAs on the formation of circulating tumor cells (CTCs) in BC and aimed to provide potential therapeutic targets, which would retain the pain-relieving effects of MORAs in BC patients without sacrificing their long-term prognosis.Different preclinical models were used to identify the effects of MORAs on the progression of BC. A novel immunocapture microfluidic chip was utilized to analyze whether MORAs affected the number of CTCs in mouse models and clinical BC patients. Bioinformatic analyses, total transcriptome sequencing, and molecular biology methods were then used to investigate the underlying mechanisms in these models and in BC cell lines.Mouse models of hematogenous metastasis and in situ BC demonstrated that tumor metastasis was significantly increased after MORA treatment. A significant increase in the number of mesenchymal and/or epithelial CTCs was detected after MORA treatment in both the mouse models and clinical trial patients. Mechanistically, MORAs facilitated the formation of CTCs by activating the MOR/PI3K/AKT/Slug signaling pathway, hereby promoting the epithelial-mesenchymal transition (EMT) of BC cells, as knockdown of MOR, Slug or blockade of PI3K inhibited the EMT process and CTC formation.MORAs promoted BC metastasis by facilitating CTC formation. The EMT-CTC axis could be targeted for preventive measures during MORA treatment to inhibit the associated tumor metastasis or recurrence in BC patients.
Design of Nanohydrogels for Targeted Intracellular Drug Transport to the Trans‐Golgi Network
Authors: Thorsten Keller, Nora Trinks, Jessica Brand, Steffen Trippmacher, Philipp Stahlhut, Krystyna Albrecht, Georg Papastavrou, Hermann Koepsell, Markus Sauer, Jürgen Groll
Journal: Advanced Healthcare Materials (2023)

Nanohydrogels combine advantages of hydrogels and nanoparticles. In particular, they represent promising drug delivery systems. Nanogel synthesis by oxidative condensation of polyglycidol prepolymers, that are modified with thiol groups, results in crosslinking by disulfide bonds. Hereby, biomolecules like the antidiabetic peptide RS1-reg, derived from the regulatory protein RS1 of the Na
Accelerated partial breast irradiation using sole interstitial multicatheter brachytherapy compared with whole-breast irradiation with boost for early breast cancer: 10-year results of a GEC-ESTRO randomised, phase 3, non-inferiority trial
Authors: Vratislav Strnad, Csaba Polgár, Oliver J Ott, Guido Hildebrandt, Daniela Kauer-Dorner, Hellen Knauerhase, Tibor Major, Jarosław Łyczek, Jose Luis Guinot, Cristina Gutierrez Miguelez, Pavel Slampa, Michael Allgäuer, Kristina Lössl, Bülent Polat, Rainer Fietkau, Annika Schlamann, Alexandra Resch, Anna Kulik, Leo Arribas, Peter Niehoff, Ferran Guedea, Jürgen Dunst, Christine Gall, Wolfgang Uter
Journal: The Lancet Oncology (2023)
Microneedle Patch Loaded with Exosomes Containing MicroRNA‐29b Prevents Cardiac Fibrosis after Myocardial Infarction
Authors: Jianping Yuan, Hong Yang, Chunxia Liu, Lianbo Shao, Haixin Zhang, Kunyan Lu, Jingjing Wang, Yuanyuan Wang, Qian Yu, Yanxia Zhang, Yunsheng Yu, Zhenya Shen
Journal: Advanced Healthcare Materials (2023)

Abstract Myocardial infarction (MI) is a cardiovascular disease that poses a serious threat to human health. Uncontrolled and excessive cardiac fibrosis after MI has been recognized as a primary contributor to mortality by heart failure. Thus, prevention of fibrosis or alleviation of fibrosis progression is important for cardiac repair. To this end, a biocompatible microneedle (MN) patch based on gelatin is fabricated to load exosomes containing microRNA‐29b (miR‐29b) mimics with antifibrotic activity to prevent excessive cardiac fibrosis after MI. Exosomes are isolated from human umbilical cord mesenchymal stem cells and loaded with miR‐29b mimics via electroporation, which can be internalized effectively in cardiac fibroblasts to upregulate the expression of miR‐29b and downregulate the expression of fibrosis‐related proteins. After being implanted in the infarcted heart of a mouse MI model, the MN patch can increase the retention of loaded exosomes in the infarcted myocardium, leading to alleviation of inflammation, reduction of the infarct size, inhibition of fibrosis, and improvement of cardiac function. This design explored the MN patch as a suitable platform to deliver exosomes containing antifibrotic biomolecules locally for the prevention of cardiac fibrosis, showing the potential for MI treatment in clinical applications.
Brain-neuron targeted nanoparticles for peptide synergy therapy at dual-target of Alzheimer's disease
Authors: Qian Guo, Yixian Li, Shuting Xu, Pengzhen Wang, Kang Qian, Peng Yang, Dongyu Sheng, Liuchang Wang, Yunlong Cheng, Ran Meng, Jinxu Cao, Haichang Luo, Yan Wei, Qizhi Zhang
Journal: Journal of Controlled Release (2023)
Nanofibers with genotyped Bacillus strains exhibiting antibacterial and immunomodulatory activity
Authors: Nina Katarina Grilc, Anže Zidar, Petra Kocbek, Tomaž Rijavec, Teja Colja, Aleš Lapanje, Matjaž Jeras, Martina Gobec, Irena Mlinarič-Raščan, Mirjana Gašperlin, Julijana Kristl, Špela Zupančič
Journal: Journal of Controlled Release (2023)

Biofilm-associated diseases such as periodontitis are widespread and challenging to treat which calls for new strategies for their effective management. Probiotics represent a promising approach for targeted treatment of dysbiosis in biofilm and modulation of host immune response. In this interdisciplinary study, nanofibers with two autochthonous Bacillus strains 27.3.Z and 25.2.M were developed. The strains were isolated from the oral microbiota of healthy individuals, and their genomes were sequenced and screened for genes associated with antimicrobial and immunomodulatory activities, virulence factors, and transferability of resistance to antibiotics. Spores of two Bacillus strains were incorporated individually or in combination into hydrophilic poly(ethylene oxide) (PEO) and composite PEO/alginate nanofibers. The nanofiber mats were characterised by a high loading of viable spores (> 7 log CFU/mg) and they maintained viability during electrospinning and 6 months of storage at room temperature. Spores were rapidly released from PEO nanofibers, while presence of alginate in the nanofibers prolonged their release. All formulations exhibited swelling, followed by transformation of the nanofiber mat into a hydrogel and polymer erosion mediating spore release kinetics. The investigated Bacillus strains released metabolites, which were not cytotoxic to peripheral blood mononuclear cells (PBMCs) in vitro. Moreover, their metabolites exhibited antibacterial activity against two periodontopathogens, an antiproliferative effect on PBMCs, and inhibition of PBMC expression of proinflammatory cytokines. In summary, the developed nanofiber-based delivery system represents a promising therapeutic approach to combat biofilm-associated disease on two fronts, namely via modulation of the local microbiota with probiotic bacteria and host immune response with their metabolites.
Targeting galectin-3 to counteract spike-phase uncoupling of fast-spiking interneurons to gamma oscillations in Alzheimer’s disease
Authors: Luis Enrique Arroyo-García, Sara Bachiller, Rocío Ruiz, Antonio Boza-Serrano, Antonio Rodríguez-Moreno, Tomas Deierborg, Yuniesky Andrade-Talavera, André Fisahn
Journal: Translational Neurodegeneration (2023)

Alzheimer's disease (AD) is a progressive multifaceted neurodegenerative disorder for which no disease-modifying treatment exists. Neuroinflammation is central to the pathology progression, with evidence suggesting that microglia-released galectin-3 (gal3) plays a pivotal role by amplifying neuroinflammation in AD. However, the possible involvement of gal3 in the disruption of neuronal network oscillations typical of AD remains unknown.Here, we investigated the functional implications of gal3 signaling on experimentally induced gamma oscillations ex vivo (20-80 Hz) by performing electrophysiological recordings in the hippocampal CA3 area of wild-type (WT) mice and of the 5×FAD mouse model of AD. In addition, the recorded slices from WT mice under acute gal3 application were analyzed with RT-qPCR to detect expression of some neuroinflammation-related genes, and amyloid-β (Aβ) plaque load was quantified by immunostaining in the CA3 area of 6-month-old 5×FAD mice with or without Gal3 knockout (KO).Gal3 application decreased gamma oscillation power and rhythmicity in an activity-dependent manner, which was accompanied by impairment of cellular dynamics in fast-spiking interneurons (FSNs) and pyramidal cells. We found that the gal3-induced disruption was mediated by the gal3 carbohydrate-recognition domain and prevented by the gal3 inhibitor TD139, which also prevented Aβ42-induced degradation of gamma oscillations. Furthermore, the 5×FAD mice lacking gal3 (5×FAD-Gal3KO) exhibited WT-like gamma network dynamics and decreased Aβ plaque load.We report for the first time that gal3 impairs neuronal network dynamics by spike-phase uncoupling of FSNs, inducing a network performance collapse. Moreover, our findings suggest gal3 inhibition as a potential therapeutic strategy to counteract the neuronal network instability typical of AD and other neurological disorders encompassing neuroinflammation and cognitive decline.
Independent Innexin Radiation Shaped Signaling in Ctenophores
Authors: Jennifer Ortiz, Yuriy V Bobkov, Melissa B DeBiasse, Dorothy G Mitchell, Allison Edgar, Mark Q Martindale, Anthony G Moss, Leslie S Babonis, Joseph F Ryan
Journal: Molecular Biology and Evolution (2023)

Abstract Innexins facilitate cell–cell communication by forming gap junctions or nonjunctional hemichannels, which play important roles in metabolic, chemical, ionic, and electrical coupling. The lack of knowledge regarding the evolution and role of these channels in ctenophores (comb jellies), the likely sister group to the rest of animals, represents a substantial gap in our understanding of the evolution of intercellular communication in animals. Here, we identify and phylogenetically characterize the complete set of innexins of four ctenophores: Mnemiopsis leidyi, Hormiphora californensis, Pleurobrachia bachei, and Beroe ovata. Our phylogenetic analyses suggest that ctenophore innexins diversified independently from those of other animals and were established early in the emergence of ctenophores. We identified a four-innexin genomic cluster, which was present in the last common ancestor of these four species and has been largely maintained in these lineages. Evidence from correlated spatial and temporal gene expression of the M. leidyi innexin cluster suggests that this cluster has been maintained due to constraints related to gene regulation. We describe the basic electrophysiological properties of putative ctenophore hemichannels from muscle cells using intracellular recording techniques, showing substantial overlap with the properties of bilaterian innexin channels. Together, our results suggest that the last common ancestor of animals had gap junctional channels also capable of forming functional innexin hemichannels, and that innexin genes have independently evolved in major lineages throughout Metazoa.
The small GTPase regulatory protein Rac1 drives podocyte injury independent of cationic channel protein TRPC5
Authors: Onur K. Polat, Elena Isaeva, Yashwanth R. Sudhini, Brenna Knott, Ke Zhu, Manuel Noben, Varsha Suresh Kumar, Nicole Endlich, Steve Mangos, Tejasree Vallapu Reddy, Beata Samelko, Changli Wei, Mehmet M. Altintas, Stuart E. Dryer, Sanja Sever, Alexander Staruschenko, Jochen Reiser
Journal: Kidney International (2023)
Low to undetectable Omicron BQ.1.1 neutralization by patient’s sera a month after initiation of AZD7442 600 mg
Authors: Franck Touret, Guillaume Martin-Blondel, Xavier de Lamballerie, Axelle Dupont, Jacques Izopet, France Mentré, Nassim Kamar, Brigitte Autran, Gilles Paintaud, Sophie Caillard, Christophe Richez, Lionel Couzi, Aliénor Xhaard, Zora Marjanovic, Jerome Avouac, Caroline Jacquet, Dany Anglicheau, Morgane Cheminant, Yazdan Yazdanpanah, Stéphanie N’Guyen, Benjamin Terrier, Jacques Eric Gottenberg, Caroline Besson, Sophie Letrou, Sabrina Kali, Denis Angoulvant, Karine Barthélémy, Stéphane Priet, Elif Nurtop, Ventzislava Petrov Sanchez, Coralie Tardivon, Gilles Blancho, Amandine Le Bourgeois, Vincent Lévy
Journal: Journal of Infection (2023)
iPSC-derived organ-on-a-chip models for personalized human genetics and pharmacogenomics studies
Authors: Victoria E.J.M. Palasantzas, Isabel Tamargo-Rubio, Kieu Le, Jelle Slager, Cisca Wijmenga, Iris H. Jonkers, Vinod Kumar, Jingyuan Fu, Sebo Withoff
Journal: Trends in Genetics (2023)

Genome-wide association studies (GWAS) have now correlated hundreds of genetic variants with complex genetic diseases and drug efficacy. Functional characterization of these factors remains challenging, particularly because of the lack of human model systems. Molecular and nanotechnological advances, in particular the ability to generate patient-specific PSC lines, differentiate them into diverse cell types, and seed and combine them on microfluidic chips, have led to the establishment of organ-on-a-chip (OoC) platforms that recapitulate organ biology. OoC technology thus provides unique personalized platforms for studying the effects of host genetics and environmental factors on organ physiology. In this review we describe the technology and provide examples of how OoCs may be used for disease modeling and pharmacogenetic research.
JAAD Case Reports Article List
Authors: Jacqueline Masehi-Lano, Hayley Leatham, Ryanne Brown, Jennifer Chen, Retiform Purpura, Bianca Kang, Joohee Han, Erik Peterson, Nikifor Konstantinov, Carly Wallace, Christopher Heath, Stephen Olsen, Jamie Jie, Min Phua, Soon Boon, Justin Wong, Nisha Chandran, May Liau, Ashley Barras, Catherine Loehr, Christopher Haas, Catherine Barker, Emily Nyers, Chelsea Kramish, Jane Scribner, Gilles Absil, Patrick Collins, Michel Reginster, Catherine Bonvoisin, Arjen Nikkels, Suzanne Xu, Katelyn Singh, Jennifer Mcniff, William Damsky, Jeffrey Gehlhausen, Zachary Bordeaux, Shawn Kwatra, Cameron West, Anna Verzı, Giuliana Caruso, Giuseppe Broggi, Giuseppe Micali, Antonio Carpinteri, Francesco Lacarrubba, Alexis Tracy, Julia Kahn, Bob Geng, Marian Russo, Bijan Safai, Michael Vittori, Jonathan Tang, William Mccoy Iv, Urmi Khanna, Yasmine Oprea, Adnan Mir, Caroline Halverstam, Amanda Walker, Ravi Patel, Travis Vandergriff, Stephanie Savory, Amy Xiao, John Miedler, Oleg Akilov, Wei Ng, Ai Koh, Mark Jean, Aan Koh, Pract Derm, Ryan Saal, Luis Borda, Robert Pariser, Francesca Genera, Faraz Yousefian, Gerard Do, Suzanne Do, Victor Friedler, Farrah Bakr, James Denny, Parastoo Babakinejad, Andrew Giles, Peloux Menage, Zoe Brown-Joel, Neda Esmaili, Sang Hong, Kara Young, Karolyn Wanat, Salma El-Behaedi, Spencer Ng, Parul Goyal, Rachel Pritzker, Jennifer Choi, Yi-Fei Xu, Zi-Qi Li, Wan-Shan Yang, Xiao-Wei Shi, Guang-Ming Han, Hagay Hayat, Dua Masarwa, Shawn Sapir, Igor Kaiserman, Sharely Milagros, Loza Canales, Francisco Gerardo, Bravo Puccio, Manuel Armando, Del Solar Chacaltana, Karina Herlinda, Feria Saldaña, Alex Leo ´n, Juan Rudy, Tico Chayña, Julianna Martel, Woo Cho, John Runge, Anisha Patel, Jean Tayar, Karin Woodman, Celyne Hume, Jonathan Curry, Meghan Heberton, David Castillo, Paolo Romanelli, Hadar Lev-Tov, Francisco Kerdel, Michael Visconti, Barry Auster, Monik Gupta, Rohun Gupta, Preeti Jhorar
Journal: Journal of the American Academy of Dermatology (2023)
Ascorbic Acid for the Common Cold
Authors: Thomas R. Karlowski
Journal: JAMA (1975)

Three hundred eleven employees of the National Institutes of Health volunteered to take 1 gm of ascorbic acid or lactose placebo in capsules three times a day for nine months. At the onset of a cold, the volunteers were given an additional 3 gm daily of either a placebo or ascorbic acid. One hundred ninety volunteers completed the study. Dropouts were defined as those who missed at least one month of drug ingestion. They represented 44% of the placebo group and 34% of those taking ascorbic acid. Analysis of these data showed that ascorbic acid had at best only a minor influence on the duration and severity of colds, and that the effects demonstrated might be explained equally well by a break in the double blind. (<i>JAMA</i>231:1038-1042, 1975)
Long-term Outcome of Episodes of Major Depression
Authors: Martin B. Keller
Journal: JAMA (1984)

Twenty-one percent (20/97) of patients with an episode of major depressive disorder and no history of chronic minor depression who sought treatment at five university medical centers had not recovered after two years of prospective follow-up. The rate of recovery was highest in the three months after entry into the study, with a notable decrease in rate after one year. Most patients who did not recover had severe depressive symptoms throughout the two years of follow-up. Long duration of episode before entry into the study, inpatient hospitalization status at entry, intact marriage, low family income, admitting research center, and a history of nonaffective psychiatric disorders (including alcoholism) predicted a chronic course. The implications of these findings for clinicians, researchers, and public health planners are discussed. (<i>JAMA</i>1984;252:788-792)
Predicting Outcome From Hypoxic-lschemic Coma
Authors: David E. Levy
Journal: JAMA (1985)

Outcome from coma caused by cerebral hypoxia-ischemia (eg, cardiac arrest) was compared with serial neurological findings in 210 patients. Thirteen percent of patients regained independent function at some point during the first postarrest year. Computer application of new multivariate techniques to the prospectively observed findings generated easily utilized rules that classified patients by likely outcome. At the time of initial examination, 52 patients (one fourth of the total population) had absent pupillary light reflexes, and none of these patients ever regained independent daily function. By contrast, the initial presence of pupillary light reflexes, the development of spontaneous eye movements that were roving conjugate or better, and the findings of extensor, flexor, or withdrawal responses to pain identified a smaller group of 27 patients, 11 (41%) of whom regained independence in their daily lives. By 24 hours after onset, 93 poor-outcome patients were identified by motor responses that were absent, extensor, or flexor and by spontaneous eye movements that were neither orienting nor roving conjugate; only one regained independent function. This contrasts with recovery in 19 (63%) of 30 patients who at that time showed improvement in their eye-opening responses and obeyed commands or had motor responses that were withdrawal or localizing. Similarly simple rules distinguished between good- and poor-prognosis patients on postarrest days 3, 7, and 14. (<i>JAMA</i>1985;253:1420-1426)